Activation of the TGF-β1/Smads/α-SMA pathway is related to histological and functional changes in children with neurogenic bladder

Sci Rep. 2022 Jun 3;12(1):9285. doi: 10.1038/s41598-022-13470-0.

Abstract

This research is to investigate the expression of the TGF-β1/Smads/α-SMA pathway and its effect on bladder histology and function in children with neurogenic bladder (NB). The bladder specimens from 10 children with NB and 8 children with vesicoureteral junction obstruction were collected into the NB and control groups. The expression of TGF-β1, Smad2, Smad3, Smad4, Smad6, α-SMA, fibronectin, collagen I and collagen III in bladder tissues was detected. In addition, the histological characteristics of the bladder were evaluated. A preoperative urodynamic study was performed on all children with NB. We analysed the correlations among the expression of the marker protein a-SMA in myofibroblasts, effector cells of the pathway, and bladder function parameters. Compared with those in the control group, the expression of TGF-β1, Smad2, Smad3, Smad4, α-SMA, fibronectin, collagen I and collagen III was significantly increased in the NB group, while the expression of Smad6 was decreased (p < 0.01). HE and Masson staining in the NB group showed increased collagen levels and hypertrophy of smooth muscle cells. Children with NB had a low bladder volume ratio (BVR), low compliance (△C) and high maximum bladder pressure, low maximum flow rate, large postvoid residual volume, low bladder contraction index and low bladder voiding efficiency. The expression of α-SMA was negatively correlated with the BVR (r = - 0.7066, P = 0.0223) and △C (r = - 0.6516, P = 0.0412). We conclude that the TGF-β1/Smads/α-SMA pathway is activated in the bladder tissue of children with NB and may be involved in the processes causing histological and functional changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Child
  • Collagen / metabolism
  • Collagen Type I / metabolism
  • Fibronectins / metabolism
  • Humans
  • Signal Transduction
  • Smad Proteins / metabolism
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1* / metabolism
  • Urinary Bladder, Neurogenic*

Substances

  • ACTA2 protein, human
  • Actins
  • Collagen Type I
  • Fibronectins
  • Smad Proteins
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Collagen